6r7k
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==Ligand complex of RORg LBD== | |
| + | <StructureSection load='6r7k' size='340' side='right'caption='[[6r7k]], [[Resolution|resolution]] 1.54Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6r7k]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6R7K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6R7K FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=JUH:(2~{R})-2-(4-ethylsulfonylphenyl)-~{N}-[4-[1,1,1,3,3,3-hexakis(fluoranyl)-2-oxidanyl-propan-2-yl]phenyl]-2-(2-phenylethanoylamino)ethanamide'>JUH</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6r7k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r7k OCA], [http://pdbe.org/6r7k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6r7k RCSB], [http://www.ebi.ac.uk/pdbsum/6r7k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6r7k ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/RORG_HUMAN RORG_HUMAN]] Possible nuclear receptor for hydroxycholesterols, the binding of which strongly promotes coactivators recruitment. Essential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes. Involved in lineage specification of uncommitted CD4(+) T-helper cells into Th17 cells. Regulate the expression of several components of the circadian clock. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The further optimization of a recently disclosed series of inverse agonists of the nuclear receptor RORC2 is described. Investigations into the left-hand side of compound 1, guided by X-ray crystal structures, led to the substitution of the 4-aryl-thiophenyl residue with the hexafluoro-2-phenyl-propan-2-ol moiety. This change resulted in to compound 28, which combined improved drug-like properties with good cell potency and a significantly lower dose, using an early dose to man prediction. Target engagement in vivo was demonstrated in the thymus of mice by a reduction in the number of double positive T cells after oral dosing. | ||
| - | + | Discovery of Potent and Orally Bioavailable Inverse Agonists of the Retinoic Acid Receptor-Related Orphan Receptor C2.,von Berg S, Xue Y, Collins M, Llinas A, Olsson RI, Halvarsson T, Lindskog M, Malmberg J, Jirholt J, Krutrok N, Ramnegard M, Brannstrom M, Lundqvist A, Lepisto M, Aagaard A, McPheat J, Hansson EL, Chen R, Xiong Y, Hansson TG, Narjes F ACS Med Chem Lett. 2019 May 29;10(6):972-977. doi:, 10.1021/acsmedchemlett.9b00158. eCollection 2019 Jun 13. PMID:31223457<ref>PMID:31223457</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6r7k" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
[[Category: Aagaard, A]] | [[Category: Aagaard, A]] | ||
| - | [[Category: | + | [[Category: Berg, S von]] |
| - | + | ||
[[Category: Narjes, F]] | [[Category: Narjes, F]] | ||
| + | [[Category: Xue, Y]] | ||
| + | [[Category: Rorg ligand]] | ||
| + | [[Category: Structure-based design]] | ||
| + | [[Category: Transcription]] | ||
Current revision
Ligand complex of RORg LBD
| |||||||||||
